title: Identification of a Steap3 endosomal targeting motif essential for normal iron metabolism.
abstract: Hereditary forms of iron-deficiency anemia, including animal models, have taught us much about the normal physiologic control of iron metabolism. However, the discovery of new informative mutants is limited by the natural mutation frequency. To address this limitation, we have developed a screen for heritable abnormalities of red blood cell morphology in mice with single-nucleotide changes induced by the chemical mutagen ethylnitrosourea (ENU). We now describe the first strain, fragile-red, with hypochromic microcytic anemia resulting from a Y228H substitution in the ferrireductase Steap3 (Steap3(Y288H)). Analysis of the Steap3(Y288H) mutant identifies a conserved motif required for targeting Steap3 to internal compartments and highlights how phenotypic screens linked to mutagenesis can identify new functional variants in erythropoiesis and ascribe function to previously unidentified motifs.
authors.affiliation: Henry Wellcome Building for Molecular Physiology, Oxford University, Oxford, United Kingdom.
authors.forename: Teresa
authors.initials: T
authors.lastname: Lambe
authors.forename: Robert J
authors.initials: RJ
authors.lastname: Simpson
authors.forename: Sara
authors.initials: S
authors.lastname: Dawson
authors.forename: Tiphaine
authors.initials: T
authors.lastname: Bouriez-Jones
authors.forename: Tanya L
authors.initials: TL
authors.lastname: Crockford
authors.forename: Michelle
authors.initials: M
authors.lastname: Lepherd
authors.forename: Gladys O
authors.initials: GO
authors.lastname: Latunde-Dada
authors.forename: Hannah
authors.initials: H
authors.lastname: Robinson
authors.forename: Kishor B
authors.initials: KB
authors.lastname: Raja
authors.forename: Dean R
authors.initials: DR
authors.lastname: Campagna
authors.forename: Guadalupe
authors.initials: G
authors.lastname: Villarreal
authors.forename: J Clive
authors.initials: JC
authors.lastname: Ellory
authors.forename: Christopher C
authors.initials: CC
authors.lastname: Goodnow
authors.forename: Mark D
authors.initials: MD
authors.lastname: Fleming
authors.forename: Andrew T
authors.initials: AT
authors.lastname: McKie
authors.forename: Richard J
authors.initials: RJ
authors.lastname: Cornall
mesh_terms: D018798:Anemia, Iron-Deficiency / Q000235:genetics* / Q000378:metabolism* / Q000503:physiopathology; D000818:Animals; D018797:Cell Cycle Proteins; D002460:Cell Line; D011992:Endosomes / Q000378:metabolism; D038181:FMN Reductase / Q000378:metabolism; D015723:Gene Library; D005820:Genetic Testing / Q000379:methods; D006801:Humans; D007501:Iron / Q000378:metabolism*; D007668:Kidney / Q000166:cytology; D008565:Membrane Proteins / Q000235:genetics* / Q000378:metabolism*; D051379:Mice; D008810:Mice, Inbred C57BL; D008817:Mice, Mutant Strains; D016296:Mutagenesis; D010088:Oxidoreductases
chemical_list: D018797:Cell Cycle Proteins; D008565:Membrane Proteins; D007501:Iron; D010088:Oxidoreductases; C473329:TSAP6 protein, mouse; D038181:FMN Reductase; C023903:ferric citrate iron reductase